There are several methods known in the art for controlling the release from a silicone rubber matrix. One method is incorporate a water soluble additives such as polyethylene, ethylene glycol, glycerol, or lactose into the silicone rubber matrix. The water soluble additive affects the swelling of the silicone rubber matrix and thereby provides a means for controlling the release of the drug or active. JP 59044310 discloses a composition comprising a silicone rubber base, an active ingredient and a powdered dissolution assistant. The powdered dissolution assistants include monobasic alpha-amino acids (glycine and alanine), sodium chloride or mannitol. The compositions disclosed in JP 59044310 are useful for implantation or insertion into the body and can release the active ingredient over a period of one week to one month.
Carelli et al. have evaluated the effects of various agents on swelling of a silicone rubber matrix with or without varying amounts of specific drugs. In "Effect of Different Water-Soluble Additives on the Sustained Release of Sulfanilamide from Silicone Rubber Matrices" IL Farmaco Edizione Pratica, 37(12), pp. 377-389 (1982) Catelli et al. evaluated the effects of ethylene glycol, glycerol, polyethylene glycols, polysorbate 80, sodium chloride and sodium alginate to release sulfanilamide from a medical grade silicone rubber to an isotonic pH 7.4 phospate buffer at controlled rates. Additionally, in "Effect of Different Water-Soluble Additive on Water Sorption into Silicone Rubber" Journal of Pharmaceutical Sciences, Bol. 73, No. 3, pp. 316-317 (1983) Catelli et al. evaluated the ability of ethylene glycol, glycerin, polyethylene glycols, polysorbate 80 and lactose dispersed individually in silicone rubber to promote water sorption into the polymer.
Another method for controlling the release of a drug from a silicone rubber matrix is by controlling the amount, type and particle size of the drug loaded into the silicone rubber matrix. For example, in "Release of Osmotically Active Drugs from Silicone Rubber Matrixes", IL Farmaco Edizione Pratica, 39(9), pp. 310-319 (1984) Catelli et al. evaluated the release of osmotically active drugs (sodium salicylate and lidocaine hydrochloride) dispersed in a silicone rubber matrix from the water swollen matrix to isotonic pH 7.4 phosphate buffer. Carelli et al. theorize that the release is via a self-triggered osmotic pumping mechanism via cracks having formed in the stressed polymer.
It is an object of the instant invention to provide a method for controlling the release of active agents or drugs from a silicone rubber matrix by controlling the cross-link density of the silicone rubber matrix.